The long-term objective of this competitive renewal application remains to delineate the genetic and environmental factors in the generation of auto antibodies in rheumatoid arthritis (RA). The current proposal is to continue to investigate the specificities of rheumatoid factors (RF) secreted by EBV transformed B cell lines and human hybridomas generated form synovial tissues and peripheral blood of RA and other patients. Special efforts will be centered on the groups of IgM RF specific for rabbit IgG, IgM RF specific for human IgG and the IgM and IgG RF which are reactive with both human and rabbit IgG. Fine specificities will be determined so that these RF can be grouped accordingly. The V region usage by RF of similar specificity from different individuals will be determined by sequencing the cDNA encoding these antibodies. These experiments intend to identify unique specificities of RF and related antibodies in RA and to test the hypothesis that similar V regions will be used by RF with similar reactivities. The high prevalence of anti- Beta hemolytic streptococcal antibodies secreted by B cell lines derived from RA synovial B cells will be confirmed. The reactive Ag of these anti-streptococcal antibody will be determined. The relationship between these antibodies and those reactive with both IgG Fc and streptococcal antigen will be investigated The supernatants of a large panel of EBV- transformed B cell lines from RA synovium and blood will be screened for antibody activities against collagens and heat-shock proteins, both of which has been implicated in the pathogenesis of RA. Hybridomas will be generated from these B cells and their V regions will be determined. The supernatants will also be used to screen cartilage and synovium. The reactive antigens will be identified. The V regions of selected antibodies with chondrocytes and synovial cells will be determined. These experiments may provide clues as to the inciting antigens and the genetic factors in RF generation as well as new information regarding autoantigens important in RA joints. They may also provide some clue to the pathogenetic agents in RA.